[unreadable] The goal of this application is to continue the development of Behavioral Naltrexone Therapy (BNT) to maximize the effectiveness of naltrexone treatment for opiate dependence. Opiate dependence is a serious public health problem, involving substantial functional impairment and risks such as fatal overdose, HIV and viral hepatitis. Antagonist maintenance with naltrexone is a theoretically promising treatment alternative, since it blocks the effects of heroin and other opiates, but itself has no opiate-like effects. However, its effectiveness has been severely limited by the transition from opiates to naltrexone, which may precipitate withdrawal, and high dropout rates during maintenance-The blockade wears off quickly after stopping oral naltrexone, and if opiate use is resumed, dependence is rapidly reestablished. In prior funding periods Behavioral Naltrexone Therapy (BNT) was developed to address these limitations. BNT incorporates a hospital-based naltrexone induction to minimize withdrawal discomfort, and blends elements of evidence based behavioral treatments (Motivational, Relapse Prevention, voucher contingencies, a significant other as medication monitor, and social skills-building) chosen to address the challenges posed by establishing compliance with daily naltrexone pill taking and abstinence. In a Stage 1b trial BNT produced treatment retention superior to a control modeling standard medical management, and a Stage 2 trial is underway. However, dropout rates remain high with just over 20% of patients completing 6 months of treatment. Trials at other centers have similarly shown behavioral therapies to improve retention on naltrexone compared to controls, but also with substantial dropout. At the same time, our group has generated promising data on a new depot formulation of naltrexone, which produces good blood levels and blockade of opiate effects for at least 4 weeks after subcutaneous injection, and retention in treatment of 68% at 2 months when combined with standard relapse prevention. This is potentially a substantial advance because it circumvents the threat of daily non-adherence to pill-taking, and the focus of concurrent behavioral therapy can shift to compliance with monthly injections. We have therefore adapted BNT to support maintenance on depot naltrexone (Depot-BNT) and now propose a Stage 1b trial in which 60 opiate-dependent patients will be randomly assigned for 6 months to either Depot-BNT, or the previously established model of BNT with oral naltrexone (BNT-Oral). The aims are to provide a preliminary test of the efficacy of Depot-BNT, and experience upon which to base revisions prior to further testing. Ultimately, it is hoped that the combination of depot naltrexone with behavioral therapy may produce outcomes approaching agonist maintenance and offer the field a viable new treatment alternative applicable to a broad range of opiate dependent patients. [unreadable] [unreadable] [unreadable] [unreadable]